What is the clinical significance of 1,25-dihydroxyvitamin D (1,25(OH)2D) levels in relation to vitamin D?

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Last updated: April 25, 2025View editorial policy

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From the Guidelines

Vitamin D supplementation with either vitamin D2 (ergocalciferol) or vitamin D3 (cholecalciferol) is recommended for patients with chronic kidney disease (CKD) to prevent nutritional vitamin D deficiency and insufficiency, especially in those with GFR of 20 to 60 mL/min/1.73 m2. The production of 1,25-dihydroxyvitamin D, the active form of vitamin D, is altered in CKD patients due to impaired kidney function, making them more susceptible to vitamin D deficiency [ 1 ]. Several factors contribute to low levels of 25(OH)D in CKD patients, including reduced exposure to sunlight, lower intake of vitamin D-rich foods, and impaired endogenous synthesis of vitamin D3 in the skin [ 1 ].

Key Points to Consider:

  • CKD patients are at a higher risk of vitamin D deficiency due to various factors, including reduced sunlight exposure and lower dietary intake of vitamin D-rich foods [ 1 ].
  • The correlation between 1,25(OH)2D levels and 25(OH)D levels in CKD patients suggests that 1,25(OH)2D levels may be more dependent on the availability of 25(OH)D in these patients [ 1 ].
  • Supplementation with vitamin D2 or vitamin D3 can help prevent vitamin D deficiency and insufficiency in CKD patients [ 1 ].
  • In patients with kidney failure (Stage 5) or those on dialysis, the need for vitamin D supplementation is less certain, but 25(OH)D levels below 15 ng/mL are associated with greater severity of secondary hyperparathyroidism [ 1 ].

Recommendations for Practice:

  • Assess CKD patients for vitamin D deficiency and insufficiency, especially those with GFR of 20 to 60 mL/min/1.73 m2.
  • Consider supplementation with vitamin D2 or vitamin D3 for CKD patients with nutritional vitamin D deficiency or insufficiency.
  • Monitor 25(OH)D levels and adjust supplementation as needed to maintain adequate levels.

From the Research

Vitamin D and 1,25 Dihydroxyvitamin D

  • Vitamin D deficiency is a significant public health concern, with severe deficiency defined as a serum 25OHD concentration below 30 nmol/l (12 ng/ml) 2.
  • The optimal serum 25OHD concentration is considered to be above 50 nmol/l (20 ng/ml) by the majority of experts, although some suggest aiming for 75 nmol/l or higher 2.
  • Vitamin D supplementation has been shown to improve musculoskeletal health, reducing the rate of fractures and falls in older adults (aged ≥ 65 yrs) with doses of 800-5000 IU/day 3.
  • The use of vitamin D supplements to prevent and treat a wide range of illnesses has increased substantially over the last decade, although the evidence for its effectiveness in preventing diseases other than musculoskeletal disorders is limited 3.

Diagnosis and Treatment of Vitamin D Deficiency

  • The diagnosis of vitamin D deficiency is typically made by measuring serum 25-hydroxyvitamin D levels, with a level below 20 ng/ml considered deficient and a level between 20-30 ng/ml considered insufficient 3.
  • Treatment of vitamin D deficiency typically involves supplementation with vitamin D, with a cumulative dose of at least 600,000 IU administered over several weeks necessary to replenish vitamin D stores in patients with documented deficiency 3.
  • The Endocrine Society recommends supplementation at suggested daily intake and tolerable upper limit levels, depending on age and clinical circumstances, and suggests measuring serum 25-hydroxyvitamin D level as the initial diagnostic test in patients at risk for deficiency 4.

Current Status and Future Directions

  • Vitamin D testing and supplementation have increased substantially in recent years, although the optimal vitamin D dose and status is still a subject of debate 5.
  • Large interventional studies have been unable to show a clear benefit of vitamin D supplementation in mostly vitamin D replete populations, highlighting the need for well-designed studies to evaluate its effectiveness 5.
  • A worldwide public health intervention that includes vitamin D supplementation in certain risk groups and systematic vitamin D food fortification to avoid severe vitamin D deficiency may be important, given its relatively wide safety margin and potential benefits 5.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Vitamin D insufficiency: Definition, diagnosis and management.

Best practice & research. Clinical endocrinology & metabolism, 2018

Research

Vitamin D deficiency 2.0: an update on the current status worldwide.

European journal of clinical nutrition, 2020

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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